Studies will be carried out further to define the mechanism of action of thyroid hormones and to describe the relationship between the occupation of nuclear sites by triiodothyronine and the generation of mRNA. Additional studies will be undertaken in hypothyroid, euthyroid and hyperthyroid animals to quantitate the content of poly (A)-containing mRNA by the application of hybridization techniques with 3H poly(dT). Sequence complexity analysis will be carried out to assess the abundancy distribution of the poly(A)-containing RNA population in various thyroid states. Further studies will be carried out to quantitate the rate of mRNA formation for specific proteins induced by T3. Studies will be undertaken to characterize more comprehensively the nature of human nuclear T3 receptor sites as obtained from surgical specimens and from maintained cadaver transplant donors. The mass of T3 and T4 specifically bound to nuclear sites in man will be quantitated and related to nuclear occupancy calculated on the basis of theoretical principles. Further studies will be undertaken to characterize the relationship between nuclear occupancy and tissue responses in man in patients under treatment for thyroid disease. Additional studies will be undertaken to quantitate the rate of change of tissue parameter in relationship to nuclear T3 content.